5.6- Dihydro-2//-1,4-oxazin-2-ones

As one would expect, oximes and nitroso-compounds are frequently encountered starting materials throughout the chemistry of this group of heterocycles. Further examples of their reactions have appeared. Reaction with enol ethers produces dihydro-oxazines (260), which may be converted to pyridine N-oxides upon treatment with HCl. Dihydro-oxazines are also obtained upon treatment of 7,6-unsaturated dicarbonyl compounds with nitrous acid. Thermolysis of these products leads to nitrones (261). 

The failure of all but 2-methyl- or 2-benzyl-dihydro-l, 3-oxazine anions to alkylate has been turned to ingenious advantage. Meyers has reported that the above two anions are stable at the generation temperature, —78 °C, but, on warming to room temperature, they rapidly rearrange to the keteni-mines (140) higher alkyl dihydro-oxazine anions form the ketenimine spontaneously at —78°C. Thus, dihydro-oxazine anions can function as nucleophiles or electrophiles, depending on the temperature employed. This has been used for the assembly of ketones with a-quaternary carbon atoms of varied structure, but specifically alkylated in one of two available sites (Scheme 64). 

The compounds with one double bond are dihydro-1,3-oxazines, and the structures shown in Fig. 1 are possible. The conformations of dihydro-1,3-oxazine rings arc based on analogy with cyclohexcne and also on the conformational analysis of several benzo-1,3-oxazine derivatives. 

Methyl-8-(2-chlorophenyl)-3,4-dihydro-177,877-pyrido[2,l-f][l,4]oxazine-7,9-carboxylate was obtained by cyclization of l,4-dihydropyridine-3,5-dicarboxylate 338 in the presence of 3M HC1 <1997CAP2188071>. Mild catalytic hydrogenation of oxazinone 339 over 5% Pd/C catalyst afforded 3,4-diphenyl-9-hydroxyperhydropyrido[2,l-f][l,4]oxazin-l-one via sequential iV-carbobenzyloxy (fV-Cbz) deprotection and reductive amination <1998TL3659>. 

Hydroxy-perhydropyrimido[2,Tr-][l,4]oxazine condensed into the pentacyclic compound 319 on heating in aqueous solution. The 9-OH-9-Me analogue did not undergo this reaction < 1996H(43) 1991 >. 7,8-Diamino-3,4-dihydro-277-pyrimido[2,1 -b [ 1,3]thiazin-6-one and 8,9-diamino-3,4-dihydro-2/7,6/7-pyrimido[6, -b][ 1,3]thiazin-6-one when reacted with benzamidine. HC1 in a melt at 220 °C in the presence of anhydrous NaOAc formed the purine derivatives 320 and 321, respectively <1996JME2529>. 

An intermediate 5-hydroxy-5,6-dihydro-2/7-pyrrolo[l,2- ][l,2]oxazin-7(4a//)-one 142 has been described in the total synthesis of (—)-loline, a pyrrolizidine alkaloid extracted from rye grass Lolium cuneatum. The key step of the synthesis was an intramolecular cycloaddition of acylnitrosodienes (obtained by in situ oxidation of the corresponding hydroxamic acids 143). This reaction generated predominantly the rro/o-stereoisomer that was further cleaved at the N-O bond with Na(Hg) and further elaborated in several steps to reach the target compound (Scheme 19) <2001J(P 1)1831 >. 

Optically pure 2,3-dihydro-6//-l, 4-oxazin-2-ones were prepared in a two-step reaction from A-protected AAs and a-bromoketones (78JOC135). When heated in boiling toluene and HCl 2,2-dimethylamino acid amides were transformed into the corresponding 3,3-dimethyl-l,4-oxazine-2,5-diones (83TL1921 87HCA329). 

Bobowsky and Shavel found an interesting intramolecular reductive transacylation reaction, in which substituted cyclopent[e][l,3]oxazin-2-ones and l,3-perhydrobenzoxazin-2-ones (90) were formed (80JHC277). In the reactions of 4-(2 -oxocycloalkyl)-3,4-dihydro-3-methyl-2//-l,3-benzoxazin-2-ones 88 and potassium borohydride, the 2 -hydroxycycloalkyl products 89 obtained underwent intramolecular transacylation reactions, resulting in the dihydro-1,3-oxazine derivatives 90. In this way, the 4-(2 -oxocycloalkyl)... 

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